Cancer Res Treat.  2005 Aug;37(4):247-250.

The Relationship between Expression of the Sodium/iodide Symporter Gene and the Status of Hormonal Receptors in Human Breast Cancer Tissue

• Oh HJ
• Chung JK
• Kang JH
• Kang WJ
• Noh DY
• Park IA
• Jeong JM
• Lee DS
• Lee MC

Abstract

PURPOSE
It has been reported that the sodium/iodide symporter (NIS) gene is expressed in several breast cancer tissues, suggesting the possibility of radionuclide imaging and therapy. However, the regulatory mechanism of NIS gene expression in breast cancer is not yet understood. To assess the relationship between the hormonal status and the NIS expression in breast cancer tissue, we investigated the NIS expression and correlated it to the expression of the thyrotropin receptor (thyroid stimulating hormone receptor, TSH-R), the estrogen receptor (ER) and the progesterone receptor (PR) in human breast cancer tissues. MATERIALS AND METHODS: Breast cancer tissues were obtained from 44 patients. Pathological examination showed 2 cases of Grade I, 17 of Grade II, 22 of Grade III, and 3 of unknown grade. We measured the expression of NIS and TSH-R genes by using RT-PCR and we measured the status of ER and PR by using immunohisto-chemistry. RESULTS: The NIS gene was expressed in 15 (34%) of the 44 breast cancer tissues. The NIS gene was expressed in 32% of the cases with TSH-R gene expression. The NIS gene was expressed in 40% of the breast cancer tissues with a positive PR and in 31% with a negative PR (p>0.05). It was positive for PR in 18% of the cases and negative for PR in 39% of the cases (p>0.05). CONCLUSION: The NIS gene is expressed in approximately one-third of the human breast cancer tissues. Its expression was not related to the presence of the TSH-R gene or hormonal receptors, ER and PR.

Keyword

Breast neoplasms; Estrogen receptors; Progesterone receptors; Sodium/iodide symporter; Thyrotropin receptors

MeSH Terms

Breast Neoplasms*
Breast*
Estrogens
Gene Expression
Humans*
Ion Transport*
Radionuclide Imaging
Receptors, Estrogen
Receptors, Progesterone
Receptors, Thyrotropin
Estrogens
Receptors, Estrogen
Receptors, Progesterone
Receptors, Thyrotropin

Figure

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  Fig. 1 Representatives of the RT-PCRs of GAPDH, NIS, and TSH-R.

Reference

1. Chung JK. Sodium iodide symporter: its role in nuclear medicine. J Nucl Med. 2002; 43:1188–1200. PMID: 12215558.

2. Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003; 24:48–77. PMID: 12588808.

3. Filetti S, Bidart JM, Arturi F, Caillou B, Russo D, Schlumberger M. Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism. Eur J Endocrinol. 1999; 141:443–457. PMID: 10576759.

4. Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, et al. Cloning of the human sodium lodide symporter. Biochem Biophys Res Commun. 1996; 226:339–345. PMID: 8806637.

5. Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, et al. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med. 2000; 6:871–878. PMID: 10932223.

6. Berghammer P, Obwegeser R, Sinzinger H. Nuclear medicine and breast cancer: a review of current strategies and novel therapies. Breast. 2001; 10:184–197. PMID: 14965584.

7. Moon DH, Lee SJ, Park KY, Park KK, Ahn SH, Pai MS, et al. Correlation between ^99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues. Nucl Med Biol. 2001; 28:829–834. PMID: 11578905.

8. Upadhyay G, Singh R, Agarwal G, Mishra SK, Pal L, Pradhan PK, et al. Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue. Breast Cancer Res Treat. 2003; 77:157–165. PMID: 12602914.

9. Kilbane MT, Ajjan RA, Weetman AP, Dwyer R, McDermott EW, O'Higgins NJ, et al. Tissue iodine content and serum-mediated ¹²⁵I uptake-blocking activity in breast cancer. J Clin Endocrinol Metab. 2000; 85:1245–1250. PMID: 10720070.

10. Kogai T, Endo T, Saito T, Miyazaki A, Kawaguchi A, Onaya T. Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells. Endocrinology. 1997; 138:2227–2232. PMID: 9165005.

11. Furlanetto TW, Nguyen LQ, Jameson JL. Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells. Endocrinology. 1999; 140:5705–5711. PMID: 10579335.

12. Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, et al. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J Clin Endocrinol Metab. 2003; 88:1880–1888. PMID: 12679487.

13. Rillema JA, Yu TX, Jhiang SM. Effect of prolactin on sodium iodide symporter expression in mouse mammary gland explants. Am J Physiol Endocrinol Metab. 2000; 279:E769–E772. PMID: 11001757.

14. Cho JY, Leveille R, Kao R, Rousset B, Parlow AF, Burak WE, et al. Hormonal regulation of radioiodide uptake activity and Na+/I- symporter expression in mammary glands. J Clin Endocrinol Metab. 2000; 85:2936–2943. PMID: 10946907.

15. Luster M, Sherman SI, Skarulis MC, Reynolds JR, Lassmann M, Hanscheid H, et al. Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2003; 30:1371–1377. PMID: 12856155.

16. Postiglione MP, Parlato R, Rodriguez-Mallon A, Rosica A, Mithbaokar P, Maresca M, et al. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland. Proc Natl Acad Sci USA. 2002; 99:15462–15467. PMID: 12432093.

17. Smyth PP, Smith DF, McDermott EW, Murray MJ, Geraghty JG, O'Higgins NJ. A direct relationship between thyroid enlargement and breast cancer. J Clin Endocrinol Metab. 1996; 81:937–941. PMID: 8772554.

18. Giani C, Fierabracci P, Bonacci R, Gigliotti A, Campani D, De Negri F, et al. Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy. J Clin Endocrinol Metab. 1996; 81:990–994. PMID: 8772562.

19. Smyth PP, Shering SG, Kilbane MT, Murray MJ, McDermott EW, Smith DF, et al. Serum thyroid peroxidase autoantibodies, thyroid volume, and outcome in breast carcinoma. J Clin Endocrinol Metab. 1998; 83:2711–2716. PMID: 9709936.

20. Dadachova E, Bouzahzah B, Zuckier LS, Pestell RG. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS). Nucl Med Biol. 2002; 29:13–18. PMID: 11786271.